Various 1-(amino-N-arylmethanethio)-3-(1-substituted benzyl-2, 3-dioxoindolin-5-yl) urea (5a-p) were designed keeping in view the structural requirements suggested in the pharmacophore model for anticonvulsant activity. Their in vivo anticonvulsant screenings were performed by two most adopted seizure models, maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ). Compound 5f was found active in MES screening while compounds 5h, 5i, 5k and 5l showed significant anticonvulsant activity in both the screenings and were devoid of any neurotoxicity. Compound 5h and 5i showed marked protection at 300 mg/kg against MES and scPTZ screening. Compound 5i also showed protection against MES screening at the dose of 100 mg/kg. In 6 Hz screening these two compounds showed significant protection and emerged as lead compounds for future investigations.

No abstract

Activity. -The anti-inflammatory activity of a series of novel synthesized chalcones (III), flavones (V) and flavanones (IV), derived from 2-hydroxyacetophenones and aromatic aldehydes is presented. The tested compounds, especially compound (IIId), show good in vitro anti-inflammatory activity compared to the reference drug indomethacin. -(BANO, S.; JAVED, K.; AHMAD, S.; RATHISH, I. G.; SINGH, S.; CHAITANYA, M.; ARUNASREE, K. M.; ALAM*, M. S.; Eur. J. Med. Chem. 65 (2013) 51-59, http://dx.

Various 2-amino-6-[3-(substituted phenyl)-5-phenyl-4,5-dihydropyrazol-1-yl]-4-(substituted phenyl)nicotinonitriles (3a-t) were designed and synthesized by clubbing two active anticonvulsant pharmacophores pyrazole and pyridine. All the synthesized compounds possessed the pharmacophoric elements essential for good anticonvulsant activity. The anticonvulsant screening was performed by maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) tests. Two compounds 3i and 3s showed significant anticonvulsant activity in both the screens with ED50 values 17.5 mg/kg and 22.6 mg/kg respectively in MES screen and 154.1 mg/kg and 242.6 mg/kg respectively in scPTZ screen. They were also found to have no acute toxic effects in mice when tested at elevated doses.

A series of 5,6-dimethoxy-2-{1-[arylamino/ alkylamino(thioxo)methyl]-4-piperidyl-methyl}-1-indanones (4a-l) were designed and synthesized by the reaction of 5,6-dimethoxy-2-(piperidin-4-yl-methyl)-indan-1-one with aryl/ alkyl isothiocyanates. The anticonvulsant activity was evaluated in animal models by maximal electroshock seizure and subcutaneous pentylenetetrazole tests. The neurotoxic effects were assessed by rotorod and ethanol potentiation tests. Gamma amino butyric acid (GABA) estimation of the selected compounds was performed in rat brain utilizing UV absorbance data. Compounds 4d, 4g, and 4j displayed encouraging anticonvulsant profile against both seizure models with remarkably lower neurotoxicity. These compounds were found to increase the GABA level in rat brain significantly.